ArticleJournal of experimental & clinical cancer research : CR2019
Heart failure drug proscillaridin A targets MYC overexpressing leukemia through global loss of lysine acetylation.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Chinese herbal medicine: Fighting SARS-CoV-2 infection on all fronts.Journal of ethnopharmacology · 2021Pooled it
- Incorporation of Organosilicon Motifs in Natural and Synthetic Small Molecules for Anticancer Therapeutics: Current Perspectives and Future Opportunities in Drug Design.Molecules (Basel, Switzerland) · 2026Review
- Deciphering Multitarget Mechanisms of Cardiac Glycosides in Acute Myeloid Leukemia Using a Network Pharmacology and Molecular Docking.Drug design, development and therapy · 2026Article
- Cell Fate Dynamics Reconstruction Identifies TPT1 and PTPRZ1 Feedback Loops as Master Regulators of Differentiation in Pediatric Glioblastoma-Immune Cell Networks.Interdisciplinary sciences, computational life sciences · 2025Article
- Semisupervised Contrastive Learning for Bioactivity Prediction Using Cell Painting Image Data.Journal of chemical information and modeling · 2025Article
- Identification and validation of CCL5 as a key gene in HIV infection and pulmonary arterial hypertension.Frontiers in cardiovascular medicine · 2024Article
- The Marine Natural Compound Dragmacidin D Selectively Induces Apoptosis in Triple-Negative Breast Cancer Spheroids.Marine drugs · 2023Article
- Cardiac glycoside ouabain efficiently targets leukemic stem cell apoptotic machinery independent of cell differentiation status.Cell communication and signaling : CCS · 2023Article
- Comparative MS- and NMR-Based Metabolome Mapping of Egyptian Red and White Squill Bulbs F. Liliaceae and in Relation to Their Cytotoxic Effect.Plants (Basel, Switzerland) · 2023Article
- Proscillaridin A inhibits lung cancer cell growth and motility through downregulation of the EGFR-Src-associated pathway.American journal of cancer research · 2023Article
- Proscillaridin A induces mitochondrial damage and autophagy in pancreatic cancer and reduces the stability of SMAD4 in Panc-1 cells.Annals of translational medicine · 2022Article
- Properties of Leukemic Stem Cells in Regulating Drug Resistance in Acute and Chronic Myeloid Leukemias.Biomedicines · 2022Review
- Article
- Proscillaridin A Sensitizes Human Colon Cancer Cells to TRAIL-Induced Cell Death.International journal of molecular sciences · 2022Article
- ANXA1 (Annexin A1) regulated by MYC (MYC proto-oncogene) promotes the growth of papillary thyroid carcinoma.Bioengineered · 2021Article
- Repurposing proscillaridin A in combination with decitabine against embryonal rhabdomyosarcoma RD cells.Cancer chemotherapy and pharmacology · 2021Article
- Emergence of Cardiac Glycosides as Potential Drugs: Current and Future Scope for Cancer Therapeutics.Biomolecules · 2021Review
- Pre-implantation alcohol exposure induces lasting sex-specific DNA methylation programming errors in the developing forebrain.Clinical epigenetics · 2021Article
- Acetylation-stabilized chloride intracellular channel 1 exerts a tumor-promoting effect on cervical cancer cells by activating NF-κB.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- Anticancer and Antiviral Properties of Cardiac Glycosides: A Review to Explore the Mechanism of Actions.Molecules (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
23 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundCardiac glycosides are approved for the treatment of heart failure as Na
methodsProscillaridin A anticancer activity was investigated against a panel of human leukemia and solid tumor cell lines with different MYC expression levels, overexpression in vitro systems and leukemia stem cells. RNA-sequencing and differentiation studies were used to characterize transcriptional and phenotypic changes. Drug-induced epigenetic changes were studied by chromatin post-translational modification analysis, expression of chromatin regulators, chromatin immunoprecipitation, and mass-spectrometry.
resultsAt a clinically relevant dose, proscillaridin A rapidly altered MYC protein half-life causing MYC degradation and growth inhibition. Transcriptomic profile of leukemic cells after treatment showed a downregulation of genes involved in MYC pathways, cell replication and an upregulation of hematopoietic differentiation genes. Functional studies confirmed cell cycle inhibition and the onset of leukemia differentiation even after drug removal. Proscillaridin A induced a significant loss of lysine acetylation in histone H3 (at lysine 9, 14, 18 and 27) and in non-histone proteins such as MYC itself, MYC target proteins, and a series of histone acetylation regulators. Global loss of acetylation correlated with the rapid downregulation of histone acetyltransferases. Importantly, proscillaridin A demonstrated anticancer activity against lymphoid and myeloid stem cell populations characterized by MYC overexpression.
conclusionOverall, these results strongly support the repurposing of proscillaridin A in MYC overexpressing leukemia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.